The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to BioMarin regarding the Biologics License Application (BLA) for valoctocogene roxaparvovec for the treatment of hemophilia A in adults. 

Valoctocogene roxaparvovec is an investigational adeno-associated virus (AAV) gene therapy that is administered as a single infusion to produce clotting factor VIII. The BLA submission included interim analysis of a phase 3 study and 3-year phase 1/2 data. Results from the ongoing phase 1/2 study showed that bleed rate control and reduction in factor VIII usage was maintained for a third year following a single administration of valoctocogene roxaparvovec. 

In the CRL, the Agency requested that the Company provide substantial evidence from its phase 3 study demonstrating durable effect using annualized bleeding rate (ABR) as the primary end point. To address these concerns, the Agency is recommending that the Company complete the phase 3 study and submit 2-year follow-up safety and efficacy data on all study patients.

According to the FDA, “the differences between Study 270-201 (phase 1/2) and the phase 3 study limited its ability to rely on the phase 1/2 study to support durability of effect.” The Company intends to meet with the Agency in the coming weeks to discuss the next steps in the approval process.

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“We are surprised and disappointed that the FDA introduced new expectations for the first time in the Complete Response Letter,” said Jean-Jacques Bienaimé, Chairman and CEO of BioMarin. “We are confident in valoctocogene roxaparvovec gene therapy and its potential to redefine the treatment paradigm for people with hemophilia A.”

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BioMarin receives Complete Response Letter (CRL) from FDA for valoctocogene Roxaparvovec gene therapy for severe hemophilia A. Accessed August 19, 2020.